The mechanisms of determinant-specific Ir gene control and of antigen recognition by T and B lymphocytes were explored at several levels in the response to myoglobin. An immunodominant epitope of myoglobin centering on Glu 109 was identified for high responder T cells restricted to I-Ad, under Ir gene control. Cloned T cell lines specific for this epitope were produced, along with clones specific for a minor epitope at Lys 140. All 109-specific clones were I-A restricted, whereas all I-E restricted clones were specific for Lys 140. Monoclonal antibodies to the Lys 140 site could block the latter clones, a novel result presumably possible because of T cell-antibody shared specificity. One clone helped B cells to make antibody in vitro. Fragment specific T cells selectively helped certain B cells, resulting in antibody only to related sites. Inhibitors of processing inhibited presentation of native myoglobin, not fragment, to the same T cell clone, implying a necessity for cleavage of the whole molecule before presentation. Anti-idiotype in vitro induced specific antibody without antigen. Syngeneic monoclonal anti-idiotypes to two monoclonal anti-myoglobins were produced. One monoclonal antibody has been partially sequenced. Alterations at the N-terminus affect antibody binding. Monoclonal antibodies can act as allosteric effectors to alter the spin state of the myoglobin heme.